1. Field of the Invention
The present invention relates to a substrate for mass spectrometry, a mass spectrometry, and a mass spectrometer. In particular, the present invention relates to a sample support substrate for mass spectrometry capable of subjecting high molecular weight analyte molecules for mass spectrometry to desorption/ionization, and capable of performing mass spectrometry easily at a high precision with less generation of complicated peaks derived from a decomposed substance and the like even in a low molecular weight region, a mass spectrometry using the substrate for mass spectrometry, and a mass spectrometer.
2. Description of the Related Art
A mass spectrometer ionizes analyte molecules by some method, applies an electric field or a magnetic field to the ionized molecules to separate the analyte molecules in accordance with a mass/charge-number (m/z), and thereafter, performs a qualitative analysis and a quantitative analysis of the analyte from a mass spectrum detected electrically. In this case, as the ionization method, there are various kinds of methods such as electronic spray ionization (ESI), electron impact ionization (EI), chemical ionization (CI), fast atom bombardment (FAB), field desorption (FD), laser desorption ionization (LDI), and matrix-assisted laser desorption ionization (MALDI). For example, in the laser ionization mass spectrometer, a sample is ionized by pulse laser light irradiation, and the ion is guided to a time-of-flight analysis portion or the like, whereby a mass spectrum and the like can be measured.
Conventionally, according to the LDI method, in a laser ionization mass spectrometer, a sample solution in which an analyte compound is dissolved in water or an organic solvent is first prepared. The sample solution is applied to a smooth surface of a metal holder, followed by drying, to form the sample into a thin film. When the sample thin film is irradiated with laser light, the laser light is absorbed by a metal sample support substrate, and the temperature increases rapidly at the irradiated portion, whereby the sample is ionized.
However, according to the above sample production method, there are problems in that a decomposition reaction (hereinafter, which may also be referred to as fragmentation) occurs simultaneously with the desorption/ionization of analyte molecules by laser light irradiation, the mass spectrum of the analyte molecules may not be obtained with a sufficient intensity, and the peak of the decomposed substance is also detected, which complicates the mass spectrum, with the result that the analysis thereof becomes difficult.
In order to solve the above problems, according to the MALDI method using, as a matrix, a mixture containing a liquid with high viscosity and low vapor pressure such as glycerin and metal fine particles (Japanese Patent Application Laid-Open No. S62-043562) or solid organic molecules such as 2,5-dihydroxybenzoic acid (DHB), sinapinic acid, and α-cyano-hydroxy-cinnamic acid (CHCA) (Japanese Patent Application Laid-Open No. H10-182704 and Japanese Patent Application Laid-Open No. 2005-326391), the matrix is desorbed/ionized by absorbing energy of irradiation laser light, and the influence of the irradiation laser light on the analyte molecules contained in the matrix is alleviated, whereby the fragmentation of the analyte molecules is suppressed, and the detection at high sensitivity can be performed. Due to the advancement of the MALDI method, even a slight amount of the analyte compound with a high molecular weight, which has not been dealt with by conventional mass spectrometry, can be measured. Thus, the MALDI method has become used widely in the analysis of a biological material and a synthetic polymer.
However, according to the MALDI method, although the decomposed substance of the analyte molecules can be suppressed considerably, a number of peaks derived from a complicated reaction occurring when the matrix itself absorbs laser light are detected, and the spectrum analysis in a low molecular weight region is still difficult in most cases. In particular, in the recent proteomix and metabolomix fields, the necessity of collectively analyzing compounds contained in blood, body fluid, and the like, as well as single molecular species, is increasing. In the case of the collective analysis, the analysis of a compound with a relatively low molecular weight with a mass number of about several hundreds, such as a substrate and a metabolite, provides important information. However, according to the conventional MALDI method, the following problem has arose: the analysis in a low molecular range cannot be performed with good precision due to the complicated peak derived from the matrix. Further, in the field of a synthetic polymer material, additives with a molecular weight of about several hundred, such as an antioxidant, a UV-absorber, and a plasticizer, are generally contained in a molded product of a polymer material, and it is also necessary to analyze the polymer material and a low molecular weight compound at a time. Thus, the complicated peak derived from the matrix in the MALDI method is an obstacle in the same way as in the collective analysis in biochemistry.
Further, in the case of analyzing a high molecular weight compound by the MALDI method, by changing measuring conditions such as intensity of irradiation laser light, for example, the fragmentation of an analyte compound can be performed actively in some cases. By analyzing fragment ions generated herein, information on the molecular structure of the analyte compound such as a substituent and a side-chain structure can also be obtained in addition to the mere analysis of a molecular weight. However, in the case where there are a number of complicated peaks derived from a matrix, the complicated peaks become a serious obstacle also in the analysis of a fragment ion from the analyte compound.
As a technology capable of performing mass analysis of the low molecular weight region simultaneously, a method of allowing analyte molecules to adhere directly to a sample support substrate having a fine porous structure on a surface thereof such as a porous silicon substrate formed by electrolytic etching, and irradiating the analyte molecules with laser light, thereby performing desorption/ionization of the analyte molecules without allowing complicated peaks derived from a matrix to appear (SALDI: surface-assisted laser desorption/ionization) is proposed (U.S. Pat. No. 6,288,390). Owing to this method, both of the efficient desorption/ionization, and the suppression of generation of a decomposed substance during the laser light irradiation can be performed. However, the upper limit of the molecular weight of the analyte compound is about several thousands, and the desorption/ionization of a compound with a molecular weight of more than several thousands is considered to be difficult.
Thus, in mass spectrometry by the desorption/ionization with the laser light irradiation it is difficult to detect collectively a low molecular weight region to a high molecular weight region at a time, and analysis in a wide molecular weight region cannot be performed.